A daily dose of oxytocin reversed osteopenia and visceral fat gain in a mouse model of menopause, researchers reported.

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The administration of oxytocin normalizes ovariectomy-induced osteopenia and bone marrow adiposity in mice.

This effect on trabecular bone parameters was mediated through the restoration of osteoblast/osteoclast cross-talk via the RANKL/OPG axis.

The daily administration of oxytocin also normalized body weight and intra-abdominal fat depots in ovariectomized mice.

A daily dose of oxytocin reversed osteopenia and visceral fat gain in a mouse model of menopause, researchers reported.

Mice that had had their ovaries removed (OVX) and received a daily dose (0.1 or 1 mg/kg) of oxytocin treatment over the course of 8 weeks had significantly reduced body weight compared with mice that received a sham operation and daily injections of a control vehicle, according to Ez-Zoubir Amri, PhD, of the Institute of Biology Valrose in Nice, France, and colleagues.

While osteoclast and osteoblast numbers decreased dramatically in the OVX mice in the 8 weeks before the start of treatment, oxytocin treatment "partially restored the osteoclast number and totally normalized the osteoblast number," they wrote online in Endocrinology.

Furthermore, oxytocin treatment in these OVX mice "induced a partial restoration in the expression of osteoclast markers and a complete restoration in that of osteoblast markers," the researchers said.

The respiratory exchange ratio was also significantly lower in treated OVX mice compared with sham mice receiving a control, "indicating that a change in fuel utilization had occurred which favored a higher rate of lipid oxidation," the researchers said.

Histological analysis of intra-abdominal and subcutaneous fat from the mice suggested that oxytocin treatment had led to a reduction of fat mass by preventing the formation of new adipocytes rather than inhibiting the size of existing ones, the researchers said.

Oxytocin treatment did not affect the body weight of sham mice, nor was there a significant effect on osteoblast or osteoclast numbers in sham mice treated with oxytocin.

These mice began receiving either a daily dose of oxytocin or a control vehicle 8 weeks after surgery, a stage at which they had already developed osteopenia and an increase in intra-abdominal fat mass. They received either oxytocin or a control for 8 weeks.

In another arm of the experiment, the researchers began oxytocin treatment on OVX or sham mice 2 weeks after surgery. "Such treatment represented potential curative therapy," the authors wrote.

In this group, OVX mice were either treated daily with 1 mg/kg of oxytocin during the first 4 weeks, and then a control vehicle for 4 weeks, or they received oxytocin twice a week for 8 weeks.

Mice receiving 4 weeks of treatment with oxytocin immediately gained weight once the oxytocin was stopped, the researchers said. Twice a week treatment "enabled a weak but not significant adipose tissue volume reduction," the researchers said.

An analysis of bone and trabecular volume suggested that OVX mice that received oxytocin twice a week were "restored" to the level of sham mice, while those that received oxytocin treatment for only 4 weeks were not.

An earlier study by the same researchers showed that plasma oxytocin levels were lower in OVX mice and rats compared with controls, and that blood levels of oxytocin were "significantly" lower in postmenopausal women who developed osteoporosis compared with women who did not.

The risk of weight gain, obesity, and osteoporosis increase with menopause. The weight gain is often in the form of visceral fat, which has been associated with an increase in risk for cardiovascular disease and cancer, among other diseases.

Though past research suggested that obesity was protective against osteoporosis, "it is now accepted that there is a negative correlation between bone and body fat mass suggesting that obesity represents a risk for osteoporosis," wrote the researchers.

Osteoporosis currently affects 40% of white postmenopausal women, and that number is expected to rise with life expectancy in the coming years, the researchers said.

Thus far the only other therapy shown to regulate intra-abdominal fat mass and bone resorption is estrogen therapy, but "the side effects of estrogens on nonfat organs hamper the possibility of using this hormone therapeutically," the researchers wrote.

"Our data clearly indicates that administration of oxytocin holds promise as a preventive therapy and may help to reverse both osteoporosis and fat mass increase," the authors wrote.

This work was supported by Centre National de la Recherche Scientifique (CNRS), Fondation pour la Recherche Médicale and the Conseil Général des Alpes-Maritimes.

Amri reported no relevant financial relationships.

Co-authors reported support by "CNRS service Partenariat et Valorisation," "Agence Nationale de la Recherche," an ATIP grant from CNRS, an equipment grant from the Région Île-de-France, an equipment grant from the University Paris Diderot-Paris 7, and a research fellowship from "Société Francophone du Diabète-Lilly."

Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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